Abstract This study aimed to analyze the physical features and effect of hydroxyapatite (HAp) and Niobium/HAp CaNb2O6/Ca3(PO4)2 composite on critical size defect in rat calvaria. Biomaterials were characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF), Particle size distribution (PSD) and Scanning Electron Microscopy (SEM). Critical size (8 mm) calvarial defects were created in Wistar rats (n = 24) distributed in three groups (90 days): Control group (CG): critical defect no treatment; HAp group: Hydroxyapatite; CNb/CPO group: CaNb2O6/Ca3(PO4)2 composite. After 90 days, calvaria samples were subjected to histological, and immunohistochemical reactions for osteopontin and osteocalcin, and Micro-CT analyses. XRD analysis confirmed the formation of a crystalline structure of CNb/CPO. XRF measurements confirmed the presence of Nb added in the sample CNb/CPO. Fracture toughness from CNb/CPO composite was 0.82 MPa.m1/2. Micro-CT showed increased trabecular number (p˂0.001), decreased porosities (%) (p˂0.001) and decreased trabecular separation (mm) (p˂0.001) in the CNb/CPO compared to CG group. In CNb/CPO group showed presence of new bone in which connective tissue differentiates to form or indicate a bone matrix score 3 (3-3.75, p˂0.05) and strong immunoexpression of osteopontin (p<0.05). The findings indicate that CNb/CPO showed resistance to the propagation of cracks and stimulated bone formation in calvaria defects in rats. (HAp NiobiumHAp Niobium CaNb2O6/Ca3PO42 CaNb2O6Ca3PO42 CaNbOCaPO CaNb2O6/Ca3 PO4 2 CaNb2O6 Ca3 CaNb O Ca PO CaNb2O6/Ca3(PO4) Xray X ray XRD, , (XRD) XRF, (XRF) PSD (PSD SEM. SEM . (SEM) 8 ( mm n 24 (9 days days) (CG) treatment Hydroxyapatite CNbCPO CNb CPO 9 histological osteocalcin MicroCT Micro CT analyses 082 0 82 0.8 MPam12 MPam MPa m1 m MPa.m1/2 p˂0.001, p0001 p p˂0.001 001 % (% (p˂0.001 (mm 33.75, 3375 3.75, 75 (3-3.75 p˂0.05 p005 05 p<0.05. p<0.05 (p<0.05) Ca3PO42 CaNb2O6/Ca3PO4 CaNb2O6Ca3PO4 CaNb2O6Ca3 CaNbOCa CaNb2O6/Ca CaNbO CaNb2O CaNb2O6/Ca3(PO4 (XRD (XRF (SEM (CG 08 0. MPam1 MPa.m1/ p000 p˂0.00 00 (p˂0.00 33 33.75 337 375 3.75 7 (3-3.7 p˂0.0 p00 p<0.0 (p<0.05 CaPO Ca3PO4 CaNb2O6/Ca3PO CaNb2O6Ca3PO CaNb2O6Ca CaNb2O6/Ca3(PO MPa.m1 (p˂0.0 33.7 37 3.7 (3-3. p˂0. p0 p<0. (p<0.0 Ca3PO MPa.m (p˂0. 33. 3. (3-3 p˂0 p<0 (p<0. (p˂0 (3- p˂ p< (p<0 (p˂ (3 (p< (p

ABSTRACT Purpose: Bioactive molecules are relevant to fight cancer and associated conditions. Quinoxaline is a privileged N-heterocycle, notably as anticancer agents. Herein, we report the evaluation of the quinoxaline derivatives DEQX and OAQX as anticancer agents, as well as in function of their anti-inflammatory and analgesic activities. Methods: Quinoxalines were synthesized and tested as anticancer agents based on cell viability and Annexin V-FITC apoptosis. Anti-inflammatory activity was evaluated from mouse carrageenan peritonitis and levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-alfa for enzyme-linked immunosorbent assay. Hot-plate and acetic acid-induced writing test were employed to investigate analgesia. Results: Both reduced the Ht-29 cell viability in a dependent-concentration manner (p < 0.001). Total apoptosis was detected for cells treated with 12.5 and 25 µg/mL of both the compounds for 24 and 48 h (all doses, p < 0.0001). DEQX (all doses, p < 0.01) and OAQX (all doses, p < 0.001) acted in leukocyte migration and decreased the IL-1β and TNF-β levels (p < 0.05). DEQX (all doses, p < 0.05) and OAQX (5mg/kg, p < 0.001) showed peripheral analgesic effect. Conclusions: In-vitro and in-vivo results suggest that these quinoxalines are promising for application in pharmacological area due to their anticancer, anti-inflammatory, and peripheric analgesia. Purpose conditions Nheterocycle, Nheterocycle N heterocycle, heterocycle N-heterocycle Herein antiinflammatory anti inflammatory activities Methods VFITC V FITC Antiinflammatory Anti IL1β ILβ IL 1β β TNFalfa TNF alfa enzymelinked enzyme linked assay Hotplate Hot plate acidinduced acid induced analgesia Results Ht29 Ht 29 Ht-2 dependentconcentration dependent concentration 0.001. 0001 0.001 . 0 001 125 12 5 12. 2 µgmL µg mL 4 all doses 0.0001. 00001 0.0001 0.0001) 0.01 01 TNFβ 0.05. 005 0.05 05 5mg/kg, 5mgkg mgkg 5mg kg mg (5mg/kg effect Conclusions Invitro In vitro invivo vivo antiinflammatory, inflammatory, Ht2 Ht- 000 0.00 00 1 0000 0.000 0.0 5mg/kg 0.

ABSTRACT Purpose: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. Methods: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. Results: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. Conclusions: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces. Purpose longchain long chain Methods n=5/group n5group ngroup n (n=5/group) 1 ip i p (i.p. 450 (45 mg/kg mgkg mg kg th day respectability L 1x109 x (1x10 CFU/mL CFUmL CFU mL i.p 5fluorouracil fluorouracil analysis chromatographymass chromatography mass Results glands signs decreased 5FU FU 182 2 (18:2 0.001 0001 0 001 181 (18:1 Conclusions 5FUinduced FUinduced induced (n=5/group (i.p 45 (4 1x10 (1x1 (18: 0.00 000 00 4 ( 1x1 (1x (18 0.0 1x (1 0.

ABSTRACT Purpose: To evaluate the effects of the experimental subcutaneous Walker-256 tumor and L-glutamine supplementation, an antioxidant, on the glomerular morphology of rats. Methods: Twenty Wistar rats were distributed into four groups (n = 5): control (C); control treated with 2% L-glutamine (CG); rats with Walker-256 tumor (WT); and rats with Walker-256 tumor treated with 2% L-glutamine (WTG). Renal histological samples were submitted to periodic acid-Schiff and Masson’s Trichrome staining to analyze glomerular density, morphometry of glomerular components and glomerulosclerosis; and to immunohistochemistry for fibroblast growth factor-2 (FGF-2). Results: WT showed 50% reduction in body mass gain and cachexia index > 10%, while WTG demonstrated reduction in cachexia (p < 0.05). WT revealed reduction of glomerular density, increase in the glomerular tuft area, mesangial area, matrix in the glomerular tuft, decrease in the urinary space and synechia, and consequently higher glomerulosclerosis (p < 0.05). L-glutamine supplementation in the WTG improved glomerular density, and reduced glomerular tuft area, urinary space, mesangial area, and glomerulosclerosis compared to WT(p < 0.05). WT showed higher collagen area and FGF-2 expression compared to C (p < 0.05). WTG presented lower collagen fibers and FGF-2 expression compared to WT (p < 0.05). Conclusions: L-glutamine supplementation reduced cachexia and was beneficial for glomerular morphology of the rats, as well as it reduced kidney damage and improved the remaining glomeruli morphology. Purpose Walker256 Walker 256 Walker-25 Lglutamine L glutamine antioxidant Methods n 5 5) (C) 2 CG (CG) (WT) WTG. . (WTG) acidSchiff acid Schiff Massons Masson s density factor2 factor factor- FGF2. FGF2 FGF (FGF-2) Results 50 10 10% p 0.05. 005 0.05 0 05 0.05) synechia WTp FGF- Conclusions Walker25 25 Walker-2 (C (CG (WT (WTG (FGF-2 1 00 0.0 Walker2 Walker- (FGF- 0. (FGF

Abstract Curcumin, contained at Turmeric (Curcumalonga), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1β and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultraviolet-visible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (p˂0.05), and decreased IL-1β (p˂0.05) and TNF-α (p˂0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.

Abstract Objective The aim of this study was to evaluate the effects of gliclazide on oxidative stress, inflammation, and bone loss in an experimental periodontal disease model. Material and Methods Male albino Wistar rats were divided into no ligature, ligature, and ligature with 1, 5, and 10 mg/kg gliclazide groups. Maxillae were fixed and scanned using micro-computed tomography to quantify linear and bone volume/tissue volume (BV/TV) and volumetric bone loss. Histopathological, immunohistochemical and immunofluorescence analyses were conducted to examine matrix metalloproteinase-2 (MMP-2), cyclooxygenase 2 (COX-2), cathepsin K, members of the receptor activator of the nuclear factor kappa-Β ligand (RANKL), receptor activator of nuclear factor kappa-Β (RANK), osteoprotegerin (OPG) pathway, macrophage migration inhibitory factor (MIF), superoxide dismutase-1 (SOD-1), glutathione peroxidase-1 (GPx-1), NFKB p 50 (Cytoplasm), NFKB p50 NLS (nuclear localization signal), PI3 kinase and AKT staining. Myeloperoxidase activity, malondialdehyde and glutathione levels, while interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. A quantitative reverse transcription polymerase chain reaction was used to quantify the gene expression of the nuclear factor kappa B p50 subunit (NF-κB p50), phosphoinositide 3-kinase (PI3k), protein kinase B (AKT), and F4/80. Results Micro-computed tomography showed that the 1 mg/kg gliclazide treatment reduced linear bone loss compared to the ligature, 5 mg/kg gliclazide, and 10 mg/kg gliclazide treatments. All concentrations of gliclazide increased bone volume/tissue volume (BV/TV) compared to the ligature group. Treatment with 1 mg/kg gliclazide reduced myeloperoxidase activity, malondialdehyde, IL-1β, and TNF-α levels (p≤0.05), and resulted in weak staining for COX-2, cathepsin k, MMP-2, RANK, RANKL, SOD-1, GPx-1,MIF and PI3k. In addition, down-regulation of NF-κB p50, PI3k, AKT, and F4/80 were observed, and OPG staining was strong after the 1 mg/kg gliclazide treatment. Conclusions This treatment decreased neutrophil and macrophage migration, decreased the inflammatory response, and decreased bone loss in rats with ligature-induced periodontitis.

Abstract Objectives: To study the intensity of inflammatory infiltrate and production of interleukin-1β (ll-1β), tumor necrosis factor-β (TNF-β), fibroblast growth factor-2 (FGF-2), glutathione peroxidase (GPX), and osteocalcin in response to in-office tooth bleaching in rats. Material and Methods: Twenty male Wistar rats were randomized into four groups (n=5) according to the received treatment (tooth bleaching or no treatment - control) and the period of euthanasia after treatment (24 h or 10 days). We performed tooth bleaching using a 38% hydrogen peroxide gel on maxillary and mandibular incisors. After euthanasia, incisors (20 per group) were processed for histological analysis, immunohistochemistry staining of ll-1β, TNF-β, FGF-2 and GPX and osteocalcin by immunofluorescence. We analyzed data using the Mann-Whitney and Kruskal-Wallis/Dunn tests (p<0.05). Results: The bleached groups presented statistically significant differences regarding the pulp inflammation stage compared with the control groups. Bleached teeth showed moderate/severe inflammatory infiltrate and control groups presented absent inflammatory cells or a negligible number of mononuclear cells (p<0.001) at two times (24 h and 10 days). There was strong staining for ll-1β, TNF-β, and GPX in bleached groups at 24 h and strong staining for ll-1β, TNF-β, GPX and FGF-2 at 10 days. After 10 days of tooth bleaching, the bleached group showed a statistically superior amount of osteocalcin than the other groups (p<0.01). Conclusions: Tooth bleaching with 38% hydrogen peroxide causes severe pulp inflammation, but characteristics of tissue repair after 10 days.

Resumo O objetivo do artigo é conhecer a distribuição e a frequência de consumo de ansiolíticos benzodiazepínicos, bem como avaliar a correlação entre consumo e características demográficas, epidemiológicas, econômicas e sociais. Estudo ecológico tendo como unidade amostral as 27 capitais brasileiras. A coleta de dados foi executada através do banco da Anvisa, para a dispensação do Alprazolam, Bromazepam, Clonazepam, Diazepam e Lorazepam, de 2010 a 2012, do Censo Demográfico 2010 (IBGE), Datasus e da pesquisa Demografia Médica. A análise estatística descritiva e a de regressão linear múltipla foram realizadas para análise dos dados. A região Norte possui as capitais com menores médias de consumo desses medicamentos e o Sudeste as mais elevadas. O consumo médio para a população de todas as capitais foi de 3,60 DHD. O Alprazolam é o mais dispensado pelas farmácias e drogarias particulares, com média de 2,00 DHD para as capitais. A análise de regressão linear múltipla demonstrou que 76% da variância do consumo foi explicada pela variação da densidade demográfica (β = 0,310 p = 0,045) e percentual de médicos (β = 0,507 p = 0,016). O consumo de ansiolíticos de meia vida curta vem crescendo ao longo dos anos, principalmente nas capitais de maior densidade demográfica e concentração de médicos.

Abstract The scope of this article is to determine the distribution and frequency of consumption of anxiolytic benzodiazepines and the correlation between consumption and demographic, epidemiological, economic and social characteristics. It is an ecological study with a sample of 27 state capitals. Data collection was performed through the ANVISA database for the dispensation of Alprazolam, Bromazepam, Clonazepam, Diazepam and Lorazepam in 2010-2012, the 2010 Demographic Census (IBGE), DATASUS and Medical Demographic Research. Descriptive statistical analysis and multiple linear regression analyses were performed for data analysis. The northern region has capitals with the lowest and the southeast has capitals with the highest average consumption of these products. The average consumption for the population of all capitals was 3.60 DHD. Alprazolam is the drug most dispensed by pharmacies and private drugstores with average 2.00 DHD for the capitals. Multiple linear regression analysis showed that 76% of the variation was explained by population density (β = 0.310 p = 0.045) and percentage of physicians (β = 0.507 p = 0.016). The consumption of short half-life anxiolytics has been on the increase, mainly in the cities of greater population density and concentration of physicians.

Resumo O objetivo do artigo é conhecer a distribuição e a frequência de consumo de ansiolíticos benzodiazepínicos, bem como avaliar a correlação entre consumo e características demográficas, epidemiológicas, econômicas e sociais. Estudo ecológico tendo como unidade amostral as 27 capitais brasileiras. A coleta de dados foi executada através do banco da Anvisa, para a dispensação do Alprazolam, Bromazepam, Clonazepam, Diazepam e Lorazepam, de 2010 a 2012, do Censo Demográfico 2010 (IBGE), Datasus e da pesquisa Demografia Médica. A análise estatística descritiva e a de regressão linear múltipla foram realizadas para análise dos dados. A região Norte possui as capitais com menores médias de consumo desses medicamentos e o Sudeste as mais elevadas. O consumo médio para a população de todas as capitais foi de 3,60 DHD. O Alprazolam é o mais dispensado pelas farmácias e drogarias particulares, com média de 2,00 DHD para as capitais. A análise de regressão linear múltipla demonstrou que 76% da variância do consumo foi explicada pela variação da densidade demográfica (β = 0,310 p = 0,045) e percentual de médicos (β = 0,507 p = 0,016). O consumo de ansiolíticos de meia vida curta vem crescendo ao longo dos anos, principalmente nas capitais de maior densidade demográfica e concentração de médicos.

Abstract The scope of this article is to determine the distribution and frequency of consumption of anxiolytic benzodiazepines and the correlation between consumption and demographic, epidemiological, economic and social characteristics. It is an ecological study with a sample of 27 state capitals. Data collection was performed through the ANVISA database for the dispensation of Alprazolam, Bromazepam, Clonazepam, Diazepam and Lorazepam in 2010-2012, the 2010 Demographic Census (IBGE), DATASUS and Medical Demographic Research. Descriptive statistical analysis and multiple linear regression analyses were performed for data analysis. The northern region has capitals with the lowest and the southeast has capitals with the highest average consumption of these products. The average consumption for the population of all capitals was 3.60 DHD. Alprazolam is the drug most dispensed by pharmacies and private drugstores with average 2.00 DHD for the capitals. Multiple linear regression analysis showed that 76% of the variation was explained by population density (β = 0.310 p = 0.045) and percentage of physicians (β = 0.507 p = 0.016). The consumption of short half-life anxiolytics has been on the increase, mainly in the cities of greater population density and concentration of physicians.

O objetivo desse trabalho foi avaliar a qualidade de cinco formulações de carbamazepina na dosagem de 200,00 mg: medicamento referência Tegretol® (Novartis), medicamento genérico (indústria nacional), medicamento similar (indústria nacional) e cápsulas do mesmo medicamento obtidas de duas farmácias de manipulação da cidade do Natal, RN. Os ensaios realizados foram: peso médio, diâmetro, espessura, teor, dissolução, desintegração, dureza, friabilidade e umidade. Foi observado que nenhuma das amostras analisadas apresentou friabilidade superior ao limite máximo determinado pela Farmacopéia Americana (1,5%). O medicamento genérico, apesar de apresentar dureza superior em relação ao medicamento de referência, desintegrou em menor tempo, o que pode estar relacionado à crospovidona presente na formulação. As amostras analisadas atenderam às especificações da Farmacopéia Brasileira no que diz respeito à dissolução. Em geral, os resultados das amostras A, B, C, D e E foram considerados satisfatórios uma vez que atenderam as especificações farmacopéicas. Embora a apresentação similar não tenha atendido ao padrão USP no que diz respeito à dureza, esse dado não se mostrou significativo, uma vez que o tempo de desintegração foi satisfatório.

The aim of this study was to evaluate the quality of five different solid formulations of carbamazepine. The reference formulation was Tegretol® 200.00 mg (Novartis) and the others were: generic formulation of carbamazepine 200.00 mg (National Industry), similar formulation of carbamazepine 200.00 mg (National Industry), and two formulations of carbamazepine 200.00 mg acquired from two different compounding pharmacies. The latter consisted of capsules obtained in Natal, the capital city of the Brazilian State of Rio Grande do Norte. The quality of samples was evaluated through physical and physical-chemical tests, including: weight, diameter, thickness, content, dissolution, disintegration, hardness, friability and moisture. The results of friability analysis showed that all formulations met Brazilian and United States Pharmacopeia (USP) specifications. In spite of having a higher hardness compared to the reference, the generic formulation had a lower disintegration time. This could be associated to the presence of crospovidone in its formulation. Results of this study showed that all formulations had dissolutions which were in accordance with Brazilian Pharmacopoeia specifications, and quality control tests. An exception was found for the similar formulation, which had a hardness parameter that exceeded the USP standard. However, this difference was not significant given the similar formulation's satisfactory disintegration time.